Encapsulation-free Controlled Release: Electrostatic Adsorption Eliminates the Need for Protein Encapsulation in PLGA Nanoparticles

Overview

Journal Sci Adv

Specialties Biology
Science

Date 2016 Jul 8

PMID 27386554

Citations 41

Authors

Malgosia M Pakulska

Irja Elliott Donaghue

Jaclyn M Obermeyer

Anup Tuladhar

Christopher K McLaughlin

Tyler N Shendruk

Molly S Shoichet

Affiliations

Soon will be listed here.

Abstract

Encapsulation of therapeutic molecules within polymer particles is a well-established method for achieving controlled release, yet challenges such as low loading, poor encapsulation efficiency, and loss of protein activity limit clinical translation. Despite this, the paradigm for the use of polymer particles in drug delivery has remained essentially unchanged for several decades. By taking advantage of the adsorption of protein therapeutics to poly(lactic-co-glycolic acid) (PLGA) nanoparticles, we demonstrate controlled release without encapsulation. In fact, we obtain identical, burst-free, extended-release profiles for three different protein therapeutics with and without encapsulation in PLGA nanoparticles embedded within a hydrogel. Using both positively and negatively charged proteins, we show that short-range electrostatic interactions between the proteins and the PLGA nanoparticles are the underlying mechanism for controlled release. Moreover, we demonstrate tunable release by modifying nanoparticle concentration, nanoparticle size, or environmental pH. These new insights obviate the need for encapsulation and offer promising, translatable strategies for a more effective delivery of therapeutic biomolecules.

Citing Articles

Electrostatic adsorptive loading of ciprofloxacin and metronidazole on chitosan nanoparticles to prolong the drug delivery process with preserved antibacterial activities: formulation and characterization.

Jahura F, Ferdousi F, Mostofa Kamal A, Ul-Hamid A, Ehsan M, Hossain M Nanoscale Adv. 2024; 7(2):621-633.

PMID: 39659765 PMC: 11626630. DOI: 10.1039/d4na00548a.

Modelling and targeting mechanical forces in organ fibrosis.

Mascharak S, Guo J, Griffin M, Berry C, Wan D, Longaker M Nat Rev Bioeng. 2024; 2(4):305-323.

PMID: 39552705 PMC: 11567675. DOI: 10.1038/s44222-023-00144-3.

Mitochondrial DNA-boosted dendritic cell-based nanovaccination triggers antitumor immunity in lung and pancreatic cancers.

Shang L, Zhao X, Huang X, Wang X, Jiang X, Kong X Cell Rep Med. 2024; 5(7):101648.

PMID: 38986624 PMC: 11293323. DOI: 10.1016/j.xcrm.2024.101648.

Immunotherapies for locally aggressive cancers.

Adams S, Nambiar A, Bressler E, Raut C, Colson Y, Wong W Adv Drug Deliv Rev. 2024; 210:115331.

PMID: 38729264 PMC: 11228555. DOI: 10.1016/j.addr.2024.115331.

Polylactic-Co-glycolic Acid Polymer-Based Nano-Encapsulation Using Recombinant Maltoporin of Aeromonas hydrophila as Potential Vaccine Candidate.

Harshitha M, Dsouza R, Disha S, Akshath U, Dubey S, Munangandu H Mol Biotechnol. 2024; 67(3):1178-1187.

PMID: 38512427 DOI: 10.1007/s12033-024-01117-6.

References

van de Weert M, Hennink W, Jiskoot W . Protein instability in poly(lactic-co-glycolic acid) microparticles. Pharm Res. 2001; 17(10):1159-67. DOI: 10.1023/a:1026498209874. View

Gupta D, Tator C, Shoichet M . Fast-gelling injectable blend of hyaluronan and methylcellulose for intrathecal, localized delivery to the injured spinal cord. Biomaterials. 2005; 27(11):2370-9. DOI: 10.1016/j.biomaterials.2005.11.015. View

Lampe K, Kern D, Mahoney M, Bjugstad K . The administration of BDNF and GDNF to the brain via PLGA microparticles patterned within a degradable PEG-based hydrogel: Protein distribution and the glial response. J Biomed Mater Res A. 2011; 96(3):595-607. DOI: 10.1002/jbm.a.33011. View

Kumar M, Bakowsky U, Lehr C . Preparation and characterization of cationic PLGA nanospheres as DNA carriers. Biomaterials. 2004; 25(10):1771-7. DOI: 10.1016/j.biomaterials.2003.08.069. View

Fredenberg S, Wahlgren M, Reslow M, Axelsson A . The mechanisms of drug release in poly(lactic-co-glycolic acid)-based drug delivery systems--a review. Int J Pharm. 2011; 415(1-2):34-52. DOI: 10.1016/j.ijpharm.2011.05.049. View

de Boer R, Knight A, Spinner R, Malessy M, Yaszemski M, Windebank A . In vitro and in vivo release of nerve growth factor from biodegradable poly-lactic-co-glycolic-acid microspheres. J Biomed Mater Res A. 2010; 95(4):1067-73. PMC: 2989534. DOI: 10.1002/jbm.a.32900. View

Ye M, Kim S, Park K . Issues in long-term protein delivery using biodegradable microparticles. J Control Release. 2010; 146(2):241-60. DOI: 10.1016/j.jconrel.2010.05.011. View

Xiong J, Narayanan J, Liu X, Chong T, Chen S, Chung T . Topology evolution and gelation mechanism of agarose gel. J Phys Chem B. 2006; 109(12):5638-43. DOI: 10.1021/jp044473u. View

Rosenfeld R, Zeni L, Haniu M, Talvenheimo J, Radka S, Bennett L . Purification and identification of brain-derived neurotrophic factor from human serum. Protein Expr Purif. 1995; 6(4):465-71. DOI: 10.1006/prep.1995.1062. View

10.

Wang Y, Wei Y, Zu Z, Ju R, Guo M, Wang X . Combination of hyaluronic acid hydrogel scaffold and PLGA microspheres for supporting survival of neural stem cells. Pharm Res. 2011; 28(6):1406-14. DOI: 10.1007/s11095-011-0452-3. View

11.

Piantino J, Burdick J, Goldberg D, Langer R, Benowitz L . An injectable, biodegradable hydrogel for trophic factor delivery enhances axonal rewiring and improves performance after spinal cord injury. Exp Neurol. 2006; 201(2):359-67. DOI: 10.1016/j.expneurol.2006.04.020. View

12.

Mollica F, Biondi M, Muzzi S, Ungaro F, Quaglia F, La Rotonda M . Mathematical modelling of the evolution of protein distribution within single PLGA microspheres: prediction of local concentration profiles and release kinetics. J Mater Sci Mater Med. 2007; 19(4):1587-93. DOI: 10.1007/s10856-007-3301-5. View

13.

Elliott Donaghue I, Tator C, Shoichet M . Sustained delivery of bioactive neurotrophin-3 to the injured spinal cord. Biomater Sci. 2015; 3(1):65-72. DOI: 10.1039/c4bm00311j. View

14.

Lai P, Everett R, Wang F, Arakawa T, GOLDWASSER E . Structural characterization of human erythropoietin. J Biol Chem. 1986; 261(7):3116-21. View

15.

Baumann M, Kang C, Stanwick J, Wang Y, Kim H, Lapitsky Y . An injectable drug delivery platform for sustained combination therapy. J Control Release. 2009; 138(3):205-13. DOI: 10.1016/j.jconrel.2009.05.009. View

16.

Bleul C, Fuhlbrigge R, Casasnovas J, Aiuti A, Springer T . A highly efficacious lymphocyte chemoattractant, stromal cell-derived factor 1 (SDF-1). J Exp Med. 1996; 184(3):1101-9. PMC: 2192798. DOI: 10.1084/jem.184.3.1101. View

17.

Makadia H, Siegel S . Poly Lactic-co-Glycolic Acid (PLGA) as Biodegradable Controlled Drug Delivery Carrier. Polymers (Basel). 2012; 3(3):1377-1397. PMC: 3347861. DOI: 10.3390/polym3031377. View

18.

Pakulska M, Vulic K, Tam R, Shoichet M . Hybrid Crosslinked Methylcellulose Hydrogel: A Predictable and Tunable Platform for Local Drug Delivery. Adv Mater. 2015; 27(34):5002-8. DOI: 10.1002/adma.201502767. View

19.

Rafati A, Boussahel A, Shakesheff K, Shard A, Roberts C, Chen X . Chemical and spatial analysis of protein loaded PLGA microspheres for drug delivery applications. J Control Release. 2012; 162(2):321-9. DOI: 10.1016/j.jconrel.2012.05.008. View

20.

Liu Y, Schwendeman S . Mapping microclimate pH distribution inside protein-encapsulated PLGA microspheres using confocal laser scanning microscopy. Mol Pharm. 2012; 9(5):1342-50. PMC: 3817562. DOI: 10.1021/mp200608y. View